3D57

TR Variant D355R

3D57 の概要

• エントリーDOI: 10.2210/pdb3d57/pdb
• 分子名称: Thyroid hormone receptor beta, [4-(4-HYDROXY-3-IODO-PHENOXY)-3,5-DIIODO-PHENYL]-ACETIC ACID, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: thyroid hormone receptor, ligand binding domain, d355r mutant, homodimer, alternative splicing, deafness, disease mutation, dna-binding, metal-binding, nucleus, polymorphism, receptor, transcription, transcription regulation, zinc, zinc-finger, hormone, transcription receptor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: P10828
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 61595.48

構造登録者

Jouravel, N. (登録日: 2008-05-15, 公開日: 2008-10-14, 最終更新日: 2023-08-30)

主引用文献

Jouravel, N.,Sablin, E.,Togashi, M.,Baxter, J.D.,Webb, P.,Fletterick, R.J.
Molecular basis for dimer formation of TRbeta variant D355R.
Proteins, 75:111-117, 2008

PubMed Abstract: Protein quality and stability are critical during protein purification for X-ray crystallography. A target protein that is easy to manipulate and crystallize becomes a valuable product useful for high-throughput crystallography for drug design and discovery. In this work, a single surface mutation, D355R, was shown to be crucial for converting the modestly stable monomeric ligand binding domain of the human thyroid hormone receptor (TR LBD) into a stable dimer. The structure of D335R TR LBD mutant was solved using X-ray crystallography and refined to 2.2 A resolution with R(free)/R values of 24.5/21.7. The crystal asymmetric unit reveals the TR dimer with two molecules of the hormone-bound LBD related by twofold symmetry. The ionic interface between the two LBDs comprises residues within loop H10-H11 and loop H6-H7 as well as the C-terminal halves of helices 8 of both protomers. Direct intermolecular contacts formed between the introduced residue Arg 355 of one TR molecule and Glu 324 of the second molecule become a part of the extended dimerization interface of 1330 A(2) characteristic for a strong complex assembly that is additionally strengthened by buffer solutes.

PubMed: 18798561
DOI: 10.1002/prot.22225

実験手法

X-RAY DIFFRACTION (2.2 Å)